ArticleNature medicine2014
Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.
4 registry-linked trialsAbstract read
In one paragraph
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 646 papers.
0numbers the graph read from it
0cells of the map it votes in
646citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A 6 Month, Open-Label, Pilot Futility Clinical Trial of Monthly Young Healthy Male Donor Plasma Transfusions for Progressive Supranuclear Palsy
The Stanford Parkinson's Disease Plasma (SPDP) Study: Intravenously-Administered Plasma From Young Donors for Treatment of Moderate Parkinson's Disease
NCT03353597 phase1 / phase2unknown statusnot on this mapstarted 2018, after this paper: background citation
Reversing Epigenetic & Other Markers of Senescence by Transfusing Young Plasma To Older Human Subjects
Safety and Efficacy of Human Umbilical Cord Blood Plasma Infusion for Age-Related Cognitive Decline
Who cites it
646 citing papers in PubMed.
- Circulating Metabolites Treat Human TMJ-OA by Eliminating Senescent Chondrocytes via the C1QBP/C1q/p14ARF Axis.Journal of extracellular vesicles · 2026Trial
- Trial
- Low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease: a randomized clinical trial.Alzheimer's research & therapy · 2025Trial
- Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial.Journal of translational medicine · 2025Trial
- Intranasal Insulin Diminishes Postoperative Delirium and Elevated Osteocalcin and Brain Derived Neurotrophic Factor in Older Patients Undergoing Joint Replacement: A Randomized, Double-Blind, Placebo-Controlled Trial.Drug design, development and therapy · 2025Trial
- Interstitial fluid rejuvenation through young-donor plasma exchange in cognitively impaired patients: a pilot safety and feasibility study.GeroScience · 2026Article
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- Article
- Core activation program and selective regional responsiveness of microglia during aging and parabiosis.Cell reports · 2026Article
- Induced pluripotent stem cell-derived macrophages (iMacs) in translational medicine: Disease models, drug testing, and therapeutic applications.Molecular biology reports · 2026Review
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
- Extracellular vesicles and epigenetic aging clocks in tissue aging: an exosome-focused conceptual framework with a focus on skin.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Review
- [Misdirected intercellular communication in aging and chronic inflammation].Zeitschrift fur Gerontologie und Geriatrie · 2026Review
- Lipidomic profiling reveals age-dependent changes in plasma membrane lipids that affect neural stem cell aging.Science advances · 2026Article
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Engineering Extracellular Vesicles for Anti-Aging Therapy: Mechanisms, Applications, and Perspectives.Aging cell · 2026Review
- Biological aging clocks in health and disease.Nature medicine · 2026Review
- Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer's Disease.International journal of molecular sciences · 2026Article
- Aged circulating CD8Immunity · 2026Article
- Plasma-based strategies for systemic rejuvenation: critical perspectives on clinical translation.GeroScience · 2026Review
586 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
18 authors.
Saul A Villeda1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Neuroscience Graduate Program, University of California San Francisco, San Francisco, California, USA. [4] Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA. [5] Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, California, USA. [6] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Kristopher E Plambeck1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3].
Jinte Middeldorp1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2].
Joseph M Castellano1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2].
Kira I Mosher1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, California, USA. [3].
Jian LuoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000000220648467
Lucas K Smith1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA.
Gregor Bieri1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [4] Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, California, USA.
Karin Lin1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Neuroscience Graduate Program, University of California San Francisco, San Francisco, California, USA.
Daniela BerdnikDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Rafael WablDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Joe Udeochu1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA.
Elizabeth G Wheatley1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, California, USA.
Bende ZouAfaSci Research Laboratory, Redwood City, California, USA.ORCID 0000000229073102
Danielle A SimmonsDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Xinmin S XieAfaSci Research Laboratory, Redwood City, California, USA.
Frank M LongoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Tony Wyss-Coray1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, California, USA. [3] Center for Tissue Regeneration, Repair and Restoration, VA Palo Alto Health Care System, Palo Alto, California, USA.
Funding
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0MSpectrum Stanford Center for clinical and Translational Research and EducationUL1TR001085 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$37.1MStanford Center for Clinical and Translational Education and Research (SCCTER)UL1UL1RR025744 · NCRR · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2008 to 2011
$22.4MTraining Program in Basic NeuroscienceT32MH020016 · NIMH · STANFORD UNIVERSITY · PI Justin L Gardner, Merritt C Maduke · 1997 to 2026
$16.2MPREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7MPREDOCTORAL TRAINING IN BIOMEDICAL SCIENCEST32GM008568 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANSEL, KARL MARK · 1995 to 2019
$6.3MRegulation of Neurogenesis and Cognition by Systemic Age-Related Immune FactorsDP5OD012178 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VILLEDA, SAUL A · 2012 to 2016
$1.8MCirculatory Rejuvenating Factors for the BrainR01AG045034 · NIA · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI WYSS-CORAY, TONY · 2013 to 2017
$1.4MRegulation of Neural Stem Cells by Changes in the Aging Systemic EnvironmentF31AG034045 · NIA · STANFORD UNIVERSITY · PI VILLEDA, SAUL A · 2009 to 2011
$88kNCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1-TR000004NCATS NIH HHS UL1 TR001085NCRR NIH HHS UL1 RR025744NCRR NIH HHS UL1-RR025744NIA NIH HHS 1F31-AG034045-01NIA NIH HHS AG03144NIA NIH HHS AG045034NIA NIH HHS F31 AG034045NIA NIH HHS R01 AG045034NICHD NIH HHS T32 HD007470NIGMS NIH HHS T32 GM008568NIH HHS DP5 OD012178NIH HHS DP5-OD1217NIMH NIH HHS T32 MH020016
Abstract
As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.
Indexed as
Age FactorsAgingAnimalsBlood TransfusionBlotting, WesternCell LineCognition DisordersCyclic AMP Response Element-Binding ProteinDNA PrimersHippocampusImmunohistochemistryMiceMice, Inbred C57BLMicroarray AnalysisNeuronal PlasticityParabiosisCyclic AMP Response Element-Binding ProteinDNA Primers
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT02460731ClinicalTrials.gov
NCT02968433ClinicalTrials.gov
NCT03353597ClinicalTrials.gov
NCT04566757ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.